In nature, prenylation and geranylation are two important metabolic processes for the creation of hemiterpenoids and monoterpenoids under enzyme catalysis. Herein, we have demonstrated bioinspired unnatural prenylation and geranylation of oxindoles using the basic industrial feedstock isoprene through ligand regulation under Pd catalysis. Pentenylated oxindoles (with C5 added) were attained with high selectivity when using a bisphosphine ligand, whereas upon switching to a monophosphine ligand, selectivity toward geranylated oxindoles (with C10 added) was achieved. Moreover, the head-to-head product could be further isomerized to an internal skipped diene under Pd-H catalysis. No stoichiometric by-product was formed in the process.

Bioinspired and Ligand-Regulated Unnatural Prenylation and Geranylation of Oxindoles with Isoprene under Pd Catalysis.

A palladium-catalyzed strategy is presented to synthesize unsymmetrically linked heterocycles within stereoselective tetrasubstituted olefins. This reaction is proposed to occur via a vinyl-PdII intermediate capable of initiating the cyclization of various alkyne-tethered nucleophiles. Products are formed in up to 96 % yield and excellent stereoselectivities are obtained using low catalyst loadings. This transformation was scalable up to 1 mmol and mechanistic studies suggest a syn-carbopalladation of the carbamoyl chloride followed by PdII -catalyzed cyclization of alkyne-tethered nucleophiles.

Accessing Unsymmetrically Linked Heterocycles through Stereoselective Palladium-Catalyzed Domino Cyclization.

Green Chemistry has become in the last two decades an increasing part of research interest. Nonconventional «green» sources for chemical reactions include micro-wave, mechanical mixing, visible light and ultrasound. 1,2,3-triazoles have important applications in pharmaceutical chemistry while their 1,2,4 counterparts are developed to a lesser extent. In the review presented here we will focus on synthesis of 1,2,3 and 1,2,4-triazole systems by means of classical and « green chemistry » conditions involving ultrasound chemistry and mechanochemistry. The focus will be on compounds/scaffolds that possess biological/pharmacophoric properties. Finally, we will also present the formal cycloreversion of 1,2,3-triazole compounds under mechanical forces and its potential use in biological systems.

Synthesis of Biologically Relevant 1,2,3- and 1,3,4-Triazoles: From Classical Pathway to Green Chemistry.

Pathways for direct conversion of indoles to oxindoles have accumulated considerable interest in recent years due to their significance in the clear comprehension of various pathogenic processes in humans and the multipotent therapeutic value of oxindole pharmacophores. Heme enzymes are predominantly responsible for this conversion in biology and are thought to proceed with a compound-I active oxidant. These heme-enzyme-mediated indole monooxygenation pathways are rapidly emerging therapeutic targets; however, a clear mechanistic understanding is still lacking. Additionally, such knowledge holds promise in the rational design of highly specific indole monooxygenation synthetic protocols that are also cost-effective and environmentally benign. We herein report the first examples of synthetic compound-I and activated compound-II species that can effectively monooxygenate a diverse array of indoles with varied electronic and steric properties to exclusively produce the corresponding 2-oxindole products in good to excellent yields. Rigorous kinetic, thermodynamic, and mechanistic interrogations clearly illustrate an initial rate-limiting epoxidation step that takes place between the heme oxidant and indole substrate, and the resulting indole epoxide intermediate undergoes rearrangement driven by a 2,3-hydride shift on indole ring to ultimately produce 2-oxindole. The complete elucidation of the indole monooxygenation mechanism of these synthetic heme models will help reveal crucial insights into analogous biological systems, directly reinforcing drug design attempts targeting those heme enzymes. Moreover, these bioinspired model compounds are promising candidates for the future development of better synthetic protocols for the selective, efficient, and sustainable generation of 2-oxindole motifs, which are already known for a plethora of pharmacological benefits.

Following Nature's Footprint: Mimicking the High-Valent Heme-Oxo Mediated Indole Monooxygenation Reaction Landscape of Heme Enzymes.

Presently, the major cornerstone of the research community is to develop green as well as sustainable protocols involving inexpensive catalysts and/or reagents without the usage of hazardous solvents under globally friendlier conditions in order to shelter both mankind and environment. Therefore, needless to say, there is always a supreme need to surrogate the older, costlier and unsafe strategies with the novel economically inexpensive and environmental benign ones. To this context, in recent past, oxone® (triple salt), a very cheap oxidizing agent having the chemical formula 2KHSO5 ⋅ KHSO4 ⋅ K2SO4 and enwrapped with the unique characteristics like easy handling, non-toxic, safe, eco-friendly, non-polluting, stable, and nicely soluble in water, in addition to its utility for large-scale synthesis etc. Bearing the importance of this versatile reagent in mind, we envisioned to update the recent advances made in this direction. Consequently, in this particular review article, the developments made in the arena of oxone chemistry covering from 2013 to 2020 have been revealed as no report appeared in the literature after a wonderful Chem. Rev. published by the group of Hussain in 2013. Herein, a comprehensive detail of a variety of oxidative transformations along with the complete plausible mechanistic steps have been exposed. For sure, present review would be a very helpful tool to the scientific community not only working in the area of organic synthesis but also to the researchers working in other branches of science and technologies as well. 

Mithula Shivani

Papers

Oxindole and its derivatives: A review on recent progress in biological activities.